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Leukemia (2013) 27, 226232 & 2013 Macmillan Publishers Limited All rights reserved 0887-6924/13
http://www.nature.com/LEU
Web End =www.nature.com/leu
ORIGINAL ARTICLE
Improvement in long-term outcomes with successive Total Therapy trials for multiple myeloma: are patients now being cured?
SZ Usmani1, J Crowley2, A Hoering2, A Mitchell2, S Waheed1, B Nair1, Y AlSayed1, F vanRhee1 and B Barlogie1
The concept of applying all active therapeutic agents in Total Therapy (TT) clinical trials for newly diagnosed multiple myeloma was pursued with the intent of developing curative treatment. The results of TT1 (n 231), TT2 (n 668) without or with thalidomide
and TT3 with added bortezomib (n 303) have been reported. An update with median follow-up times of 17.1, 8.7 and 5.5 years,
respectively, is provided. Conditional overall survival (OS) analysis from a 4-year landmark was applied to account for earlier protocol failure owing to disease aggressiveness and toxicities. Cumulative relative survival was computed in the context of age- and gender-matched US population, and interval-specic relative survival ratios were estimated to determine times to normal survival expectation. Based on Cox model-adjusted statistics, OS, progression-free survival and complete-response duration all improved with the transitions from TT1 to TT2 to TT3; improvement was also evident from time-to-progression estimates, 4-year conditional survival data and cumulative relative survival. Interval-specic relative survival normalized progressively sooner, reaching near-normal levels with TT3 in patients who attained complete response. Thus, a strategy using all myeloma-effective agents up-front seems effective at preventing, in progressively larger patient cohorts over time, the outgrowth of resistant tumor cells that account for ongoing relapses.
Leukemia (2013) 27, 226232; doi:http://dx.doi.org/10.1038/leu.2012.160
Web End =10.1038/leu.2012.160
Keywords: multiple myeloma; transplant; survival
INTRODUCTIONDespite major advances in therapy, multiple myeloma is still considered an incurable malignancy.1 Introduction of immunomodulatory drugs and bortezomib and advances in high-dose chemotherapy administration have improved progression-free survival (PFS) and overall survival (OS) for myeloma patients in general, but most patients suffer relapses and progressively shorter disease-free intervals with each relapse.2,3 We have reported our Total Therapy (TT) trials46 that use all active treatments up-front to achieve maximum tumor cytoreduction and thereby increase the frequency and duration of complete response (CR), with the goal of extending PFS and OS.With median follow-up times of 17.1 years for TT1, 8.7 years for TT2 and 5.5 years for...